Maoz-Segal Ramit, Levy Tanya, Haj-Yahia Soad, Offengenden Irena, Iancovich-Kidon Mona, Agmon-Levin Nancy
Clinical Immunology, Angioedema and Allergy Unit, Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel.
World Allergy Organ J. 2020 Aug 4;13(8):100448. doi: 10.1016/j.waojou.2020.100448. eCollection 2020 Aug.
Chronic Spontaneous Urticaria (CSU) is a relatively common immune mediated disease that can be effectively treated nowadays. Nevertheless, for some patients remission cannot be achieved following current treatment recommendations, defined as resistant CSU (r-CSU). Treating r-CSU is challenging, and, currently, there are no recommended interventions. In this real-life study we describe successful therapy of 18 r-CSU patients using an "intensified protocol" of anti-IgE-antibody (omalizumab) concomitantly with an immunosuppressant. We defined the r-CSU phenotype and compared it to omalizumab-responsive CSU (Or-CSU) phenotype.
Clinical and serological data of 72 CSU patients (ie, 18 r-CSU and 54 age and sex matched Or-CSU) were retrospectively collected and analyzed. All patients were diagnosed with CSU for ≥6 months and treated at the Sheba Medical Center during 2013-2018.
Of 289 CSU patients, 18 (6%) were diagnosed with r-CSU and treated with the "intensified protocol" including omalizumab and cyclosporine-A (16p), methotrexate (1p), and azathioprine (1p). Of which, 14/18 (78%) achieved complete remission, 2/18 (11%) partial remission, and 2/18 (11%) no remission. During follow-up no serious adverse events were documented. r-CSU patients received higher doses of antihistamine (p < 0.0001) and omalizumab (425 ± 58 mg/month vs. 283 ± 86 mg/month; p < 0.0001) compared to Or-CSU. The r-CSU phenotype was linked with concomitant autoimmunity (p = 0.0005) and a lower level of IgE prior to initiation of therapy (p = 0.027).
r-CSU may be a distinct CSU phenotype characterized by severe disease, concomitant autoimmunity, and lower baseline-IgE levels (low "autoallergy"). An "intensified protocol" with omalizumab and an immunosuppressive agent was found to be efficacious and safe for r-CSU. Further larger studies are required to verify these results.
慢性自发性荨麻疹（CSU）是一种相对常见的免疫介导性疾病，如今可得到有效治疗。然而，对于一些患者，按照当前治疗建议无法实现缓解，即难治性CSU（r-CSU）。治疗r-CSU具有挑战性，目前尚无推荐的干预措施。在这项真实世界研究中，我们描述了使用抗IgE抗体（奥马珠单抗）与免疫抑制剂联合的“强化方案”成功治疗18例r-CSU患者的情况。我们定义了r-CSU的表型，并将其与奥马珠单抗反应性CSU（Or-CSU）表型进行比较。
回顾性收集并分析了72例CSU患者（即18例r-CSU患者和54例年龄及性别匹配的Or-CSU患者）的临床和血清学数据。所有患者均被诊断为CSU≥6个月，并于2013年至2018年在舍巴医疗中心接受治疗。
在289例CSU患者中，18例（6%）被诊断为r-CSU，并接受了包括奥马珠单抗和环孢素A（16例）、甲氨蝶呤（1例）和硫唑嘌呤（1例）的“强化方案”治疗。其中，14/18（78%）实现完全缓解，2/18（11%）部分缓解，2/18（11%）未缓解。随访期间未记录到严重不良事件。与Or-CSU患者相比，r-CSU患者接受了更高剂量的抗组胺药（p < 0.0001）和奥马珠单抗（425±58 mg/月 vs. 283±86 mg/月；p < 0.0001）。r-CSU表型与自身免疫并存（p = 0.0005）以及治疗开始前较低的IgE水平相关（p = 0.027）。
r-CSU可能是一种独特的CSU表型，其特征为病情严重、自身免疫并存以及较低的基线IgE水平（低“自身过敏”）。发现奥马珠单抗与免疫抑制剂联合的“强化方案”对r-CSU有效且安全。需要进一步开展更大规模的研究来验证这些结果。
